Interleukin 6 and Interleukin 8 as Potential Biomarkers for Oral Cavity and Oropharyngeal Squamous Cell Carcinoma

Marcus, John; Yang, Li; Zhou, Xiaofeng; Denny, Paul; Ho, Chih Ming; Montemagno, Carlo; Shi, Wenyuan; Qi, Fengxia; Wu, Benjamin M.; Sinha, Uttam K.; Jordan, Richard C.; Wolinsky, Lawrence E.; Park, No Hee; Liu, Honghu; Abemayor, Elliot; Wong, David T.

doi:10.1001/archotol.130.8.929

Cited by 356 publications

(282 citation statements)

References 17 publications

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“…The addition of HA and IL-8 did not improve the model, though these markers have shown promise in other studies [6,13,27]. Our results do suggest that IL-8 levels are associated with more aggressive disease (lymph node metastases).…”

Section: Discussioncontrasting

confidence: 50%

“…Its soluble form (solCD44) is a major ligand for hyaluronic acid (HA). Interleukin-8 (IL-8) and total protein levels are all increased in saliva and/or oral rinses from HNSCC patients compared to controls [12,13]. Each of these markers is fairly stable and easily measured with ELISA and ELISA-like assays, detection platforms that are highly validated and widely used [14].…”

Section: Introductionmentioning

confidence: 99%

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Salivary markers and risk factor data: A multivariate modeling approach for head and neck squamous cell carcinoma detection

Pereira

Adebisi

Perez

et al. 2012

CBM

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Abstract.Background: Head and neck squamous cell carcinoma (HNSCC) is a debilitating and deadly disease largely due to late stage diagnosis. Prior work indicates that soluble CD44 (solCD44) and total protein may be useful diagnostic markers for HNSCC. In this study we combine the markers solCD44, IL-8, HA, and total protein with demographic and risk factor data to derive a multivariate logistic model that improves HNSCC detection as compared to our previous data using biomarkers alone. Methods: We performed the solCD44, IL-8, HA, and total protein assays on oral rinses from 40 HNSCC patients and 39 controls using ELISA assays. Controls had benign diseases of the upper aerodigestive tract and a history of tobacco or alcohol use. All subjects completed a questionnaire including demographic and risk factor data. Results: Depending on cancer subsite, differences between cases and controls were found for all markers. A multivariate logistic model including solCD44, total protein and variables related to smoking, oral health and education offered a significant improvement over the univariate models with an AUC of 0.853. Sensitivity ranged from 75-82.5% and specificity from 69.2-82.1% depending on predictive probability cut points. Conclusion: A multivariate model, including simple and inexpensive molecular tests in combination with risk factors, results in a promising tool for distinguishing HNSCC patients from controls. Impact: In this case-control study, the resulting observations led to an unprecedented multivariate model that distinguished HNSCC cases from controls with better accuracy than the current gold standard which includes oral examination followed by tissue biopsy. Since the components are simple, noninvasive, and inexpensive to obtain, this model combining biomarkers, risk factor and demographic data serves as a promising prototype for future cancer detection tests.

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Section: Discussioncontrasting

confidence: 50%

Section: Introductionmentioning

confidence: 99%

Salivary markers and risk factor data: A multivariate modeling approach for head and neck squamous cell carcinoma detection

Pereira

Adebisi

Perez

et al. 2012

CBM

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“…Etiologic factors for OSCC includes both a genetic predisposition (1) and exposure to carcinogens such as tobacco, alcohol, chronic inflammation, and the human papilloma virus infection (2). Previously, interleukin (IL)-6 and IL-8 have been implicated as potential biomarkers for OSCC (3). Chemokines are implicated in tumor progression and metastasis (4).…”

Section: Introductionmentioning

confidence: 99%

A Novel Function of CXCL13 to Stimulate RANK Ligand Expression in Oral Squamous Cell Carcinoma Cells

Sambandam

Griffin

Sundaram

et al. 2009

Molecular Cancer Research

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Oral squamous cell carcinomas (OSCC) are malignant tumors with a potent activity of local bone invasion/ osteolysis. The chemokine ligand, CXCL13, has been identified as a prognostic marker for OSCC development and progression. Here in, we show that recombinant hCXCL13 treatment of OSCC cells stimulates (5-fold) RANK ligand (RANKL), a critical bone resorbing osteoclastogenic factor expression. Anti-CXCR5 chemokine receptor antibody abrogates CXCL13-induced RANKL expression in these cells. Also, CXCL13 stimulated (3.0-fold) hRANKL gene promoter activity in SCC14a cells. SuperArray screening for transcription factors by real-time RT-PCR identified significant increase in the levels of c-Jun and NFATc3 mRNA expression in CXCL13-stimulated OSCC cells. CXCL13 treatment significantly increased (3.5-fold) phospho-c-Jun levels in these cells and a c-Jun-NH 2 -kinase inhibitor abolished CXCL13-stimulated RANKL expression. Furthermore, we show that CXCL13 stimulation induced nuclear translocation of NFATc3 in OSCC cells. Chromatinimmune precipitation assay confirmed NFATc3 binding to the RANKL promoter region. We also show that overexpression of NFATc3 stimulates RANKL expression/ promoter activity and that siRNA suppression of NFATc3 abolished CXCL13-stimulated RANKL expression. Thus, our results suggest that NFATc3 is a downstream target of the CXCL13/CXCR5 axis to stimulate RANKL expression in OSCC cells and implicates CXCL13 as a potential therapeutic target to prevent OSCC bone invasion/

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“…In an attempt to link IL-8 protein, a putative biomarker for oral cancer, to IL-8 RNA in the same saliva supernatant, our group discovered that human messenger RNAs are present in cellfree form in saliva [9]. Upon this finding we profiled salivary RNA of healthy subjects on gene expression arrays, establishing the "normal salivary core transcripts" (NSCT), a set of 185 mRNAs which were detected in each saliva supernatant of the studied 10 healthy subjects [10].…”

Section: Salivary Transcriptomementioning

confidence: 99%

“…• Microarray technology was applied to identify RNA profiles in cell free saliva [10] and to define a normalSalivary core transcriptome (NSCT) • Salivary mRNA biomarkers for oral cancer were identified through microarray technology as DUSP1, H3F3A, OAZ1, S100P, SAT, IL8 and IL1B [9][10][11].…”

Section: Salivary Transcriptomementioning

confidence: 99%

Salivary mRNA targets for cancer diagnostics

Zimmermann

Wong

2008

Oral Oncology

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Head and neck squamous cell carcinoma (HNSCC) affects almost 1 million people worldwide per year. Despite therapeutic advances the overall survival rate remains low because diagnosis often occurs only at advanced stages with poor prognosis. Like in most cancers, the implementation of an early detection scheme would have a positive impact on this disease. Similarly, as oral cancer has a very high recurrence rate, the early identification of recurrence or second primary tumors is an important challenge.HNSCC detection is currently based on expert clinical examination of the upper aerodigestive tract and histologic analysis of suspicious areas, but it may be undetectable in hidden sites, and unfortunately visual screening for oral lesions is an often neglected part of dental healthcare. Our group is actively pursuing the assembly of a toolbox for the molecular analysis of oral fluid. Here we present our current status utilizing the salivary transcriptome for oral cancer diagnostics.

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Interleukin 6 and Interleukin 8 as Potential Biomarkers for Oral Cavity and Oropharyngeal Squamous Cell Carcinoma

Cited by 356 publications

References 17 publications

Salivary markers and risk factor data: A multivariate modeling approach for head and neck squamous cell carcinoma detection

Salivary markers and risk factor data: A multivariate modeling approach for head and neck squamous cell carcinoma detection

A Novel Function of CXCL13 to Stimulate RANK Ligand Expression in Oral Squamous Cell Carcinoma Cells

Salivary mRNA targets for cancer diagnostics

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